Sensei Bio Presents Preclinical Data for Novel Antibody Therapeutic for Solid Tumours
Immuno-oncology company Sensei Bio has announced positive preclinical data for its headline therapeutic SNS-101. The antibody therapeutic that targets the transmembrane protein VISTA, an immune checkpoint that suppresses T cell activation.
VISTA is only active at low pHs such as in the tumour microenvironment where it is able to bind to the protein PSGL-1. Sensei’s antibody blocks the immunosuppressive interaction of VISTA with PSGL-1 in an effort to affect T cells in the TME to attack solid tumours.
Combination strategies in blocking VISTA along with other T cell checkpoint inhibitors like PD-1, PD-L1, and CTLA-4 can be highly efficacious according to preclinical data. Identifying options of blocking VISTA–PSGL-1 interaction without causing cytokine release syndrome (CRS) and target-mediated drug disposition (TMDD) were among the goals of the study.
“New crystal structure analysis further elucidates the antibody’s mechanism of action, showing that SNS-101 directly blocks the pH-dependent interaction between VISTA and PSGL-1,” said Edward van der Horst, Chief Scientific Officer of Sensei Bio.
The immuno-oncology company has said that it expects to submit an Investigational New Drug (IND) application for SNS-101 before the end of April 2023. A phase I/II clinical trial is also anticipated for 2023, subject to regulatory clearance.
Sensei showcased their data in a presentation entitled ‘Next Generation Antibody Therapeutics: From Discovery to Patient’, which van der Horst delivered. The presentation, which has been summarised as a poster on the company’s website, highlights crystal structure analysis of SNS-101 which elucidates the mechanism of action for the drug.
Furthermore, in vitro and in vivo assays suggest the drug’s lower likelihood for causing CRS and TMDD than a non-pH-dependant antibody. An expansion of both naïve and memory T cell phenotypes in vivo and enhanced antitumour effects when in combination with anti-PD-1 antibodies were also observed.
Van der Horst continued: “Together, these preclinical data support the biological rationale for our pH-dependent approach, which we believe is key to targeting active protonated VISTA with exquisite selectivity.”
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